The role of admission documents on the pricing of UK fixed priced IPOs

Using text analysis, we investigate the impact of the length of prospectuses on IPO pricing for a sample of UK Fixed Priced IPOs between 2004 and 2012 and show more information in the prospectus improves price accuracy as longer admission documents exhibit higher offer price and less underpricing. We explain the effect on the offer price as the consequence of the “pilot fishing” stage which seems to characterize a lot of UK IPOs

Size and Diversity in VC syndicates and their impact on IPO performance

This paper investigates the impact of venture capital (VC) syndicate size and composition on the IPO and post IPO performances of investee companies in an attempt to shed some light on the extent to which larger and more diverse syndicates are more likely to suffer from internal agency problems which might hinder the decision making process and lead to less value added for their portfolio companies. The question is of great relevance because, while the vast majority of the empirical literature compares VC backed IPOs with non VC backed ones, most VC funding is provided by syndicates of two or more financiers. We construct alternative measures of size as well as diversity based on several VC characteristics such as age, geographic location, type and affiliation of VC firms and find that larger and more diverse syndicates are associated with higher underpricing and lower valuation at the IPO date. Furthermore we provide evidence that that diversity and size are negatively correlated to the long term performance of the IPO firms and this finding is robust to several alternative measures of long term performance

Essays on initial public offerings

The present dissertation includes three essays on initial public offerings (IPO). The first chapter investigates the impact of venture capital (VC) syndicate size and diversity on the IPO and post-IPO performances of investee companies. We provide evidence that firms backed by larger and more diverse VC syndicates experience greater underpricing and lower post-IPO profitability. We suggest that this might be the consequence of coordination problems and conflicts of interests within large and heterogeneous VC syndicates which ultimately results in poorer added value for the investee companies. We also provide some evidence that the negative impact of VC syndicate size and diversity on IPO underpricing can be mitigated by the existence of alternative monitoring mechanisms such as bank loans. In the second essay, using text sentiment analysis, we investigate the relationship between tone, length and information content of prospectuses and underpricing in a sample of UK IPOs between 2004 and 2012. The peculiar feature of the UK IPO market is the wide use of fixed-priced offerings to go public, which, contrary to bookbuilding, does not allow any price discovery. Our results show that, for fixed-priced IPOs, the length of the admission document is positively correlated to the offer price and negatively correlated to underpricing and to ex-post volatility, whereas different tone and information content in the document seem to matter less. We further show that admission documents have become substantially longer for all types of IPOs since the recent financial crisis but that their impact on IPO pricing appears to be significant only during the pre-crisis period. The last chapter, the third essay, investigates how the market for European IPOs has changed, if at all, since the recent financial crisis. For this purpose we have constructed a comprehensive dataset of European IPOs between 2000 and 2012. Our research focuses on whether and how the costs, both direct and indirect, of going public have changed in the wake of the recent financial crisis. Our results suggest that both underpricing and underwriting fees have decreased since 2007. A closer look at the underwriting markets also shows that, since the financial crisis, underwriters have tended to syndicate more, and that there are some newcomers among the top ten underwriters. Additionally, we shed some light on the determinants of going public during post-crisis period, and we find that traditional models are of very little use in explaining IPO decisions during the recent recession

Comparing sequence and structure of falcipains and human homologs at prodomain and catalytic active site for malarial peptide-based inhibitor design:

Falcipains are major cysteine proteases of Plasmodium falciparum involved in haemoglobin degradation and remain attractive anti-malarial drug targets. Several inhibitors against these proteases have been identified, yet none of them has been approved for malaria treatment. Other Plasmodium species also possess highly homologous proteins to falcipains. For selective therapeutic targeting, identification of sequence and structure differences with homologous human cathepsins is necessary. The substrate processing activity of these proteins is tightly controlled via a prodomain segment occluding the active site which is chopped under low pH conditions exposing the catalytic site. Current work characterizes these proteases to identify residues mediating the prodomain regulatory function for the design of peptide based anti-malarial inhibitors

Structure based docking and molecular dynamic studies of plasmodial cysteine proteases against a South African natural compound and its analogs:

Identification of potential drug targets as well as development of novel antimalarial chemotherapies with unique mode of actions due to drug resistance by Plasmodium parasites are inevitable. Falcipains (falcipain-2 and falcipain-3) of Plasmodium falciparum, which catalyse the haemoglobin degradation process, are validated drug targets. Previous attempts to develop peptide based drugs against these enzymes have been futile due to the poor pharmacological profiles and susceptibility to degradation by host enzymes. This study aimed to identify potential non-peptide inhibitors against falcipains and their homologs from other Plasmodium species

Distinct regulation of tonsillar immune response in virus infection

Cataloged from PDF version of article.Background: The relationships between tonsillar immune responses, and viral infection and allergy are incompletely known. Objective To study intratonsillar/nasopharyngeal virus detections and in vivo expressions of T-cell- and innate immune response-specific cytokines, transcription factors, and type I/II/III interferons in human tonsils. Methods: Palatine tonsil samples were obtained from 143 elective tonsillectomy patients. Adenovirus, bocavirus-1, coronavirus, enteroviruses, influenza virus, metapneumovirus, parainfluenza virus, rhinovirus, and respiratory syncytial virus were detected using PCR. The mRNA expression levels of IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2, and Tbet were directly analyzed by quantitative RT-PCR. Results Fifty percentage of subjects reported allergy, 59% had ≥1 nasopharyngeal viruses, and 24% had ≥1 intratonsillar viruses. Tonsillar virus detection showed a strong negative association with age; especially rhinovirus or parainfluenza virus detection showed positive association with IFN-γ and Tbet expressions. IL-37 expression was positively associated with atopic dermatitis, whereas IFN-α, IL-13, IL-28, and Tbet expressions were negatively associated with allergic diseases. Network analyses demonstrated strongly polarized clusters of immune regulatory (IL-10, IL-17, TGF-β, FOXP3, GATA3, RORC2, Tbet) and antiviral (IFN-α, IFN-β, IL-28, IL-29) genes. These two clusters became more distinctive in the presence of viral infection or allergy. A negative correlation between antiviral cytokines and IL-10, IL-17, IL-37, FOXP3, and RORC2 was observed only in the presence of viruses, and interestingly, IL-13 strongly correlated with antiviral cytokines. Conclusions: Tonsillar cytokine expression is closely related to existing viral infections, age, and allergic illnesses and shows distinct clusters between antiviral and immune regulatory genes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Impact of emerging mutations on the dynamic properties the SARS-CoV-2 main protease: an in silico investigation

The new coronavirus (SARS-CoV-2) is a global threat to world health and its economy. Its main protease (Mpro), which functions as a dimer, cleaves viral precursor proteins in the process of viral maturation. It is a good candidate for drug development owing to its conservation and the absence of a human homolog. An improved understanding of the protein behaviour can accelerate the discovery of effective therapies in order to reduce mortality. 100 ns all-atom molecular dynamics simulations of 50 homology modelled mutant Mpro dimers were performed at pH 7 from filtered sequences obtained from the GISAID database. Protease dynamics were analysed using RMSD, RMSF, Rg, the averaged betweenness centrality and geometry calculations. Domains from each Mpro protomer were found to generally have independent motions, while the dimer-stabilising N-finger region was found to be flexible in most mutants

SANCDB: a South African natural compound database

Natural products (NPs) are important to the drug discovery process. NP research efforts are expanding world-wide and South Africa is no exception to this. While freely-accessible small molecule databases, containing compounds isolated from indigenous sources, have been established in a number of other countries, there is currently no such online database in South Africa

Analysis of non-peptidic compounds as potential malarial inhibitors against Plasmodial cysteine proteases via integrated virtual screening workflow

Falcipain-2 (FP-2) and falcipain-3 (FP-3), haemoglobin-degrading enzymes in Plasmodium falciparum, are validated drug targets for the development of effective inhibitors against malaria. However, no commercial drug-targeting falcipains has been developed despite their central role in the life cycle of the parasites. In this work, in silico approaches are used to identify key structural elements that control the binding and selectivity of a diverse set of non-peptidic compounds onto FP-2, FP-3 and homologues from other Plasmodium species as well as human cathepsins. Hotspot residues and the underlying non-covalent interactions, important for the binding of ligands, are identified by interaction fingerprint analysis between the proteases and 2-cyanopyridine derivatives (best hits). It is observed that the size and chemical type of substituent groups within 2-cyanopyridine derivatives determine the strength of protein–ligand interactions. This research presents novel results that can further be exploited in the structure-based molecular-guided design of more potent antimalarial drugs.http://www.tandfonline.com/loi/tbsd20hb2017Forestry and Agricultural Biotechnology Institute (FABI)Genetic